EE03973B1 - Factor Xa inhibitors - Google Patents

Factor Xa inhibitors

Info

Publication number
EE03973B1
EE03973B1 EE9600146A EE9600146A EE03973B1 EE 03973 B1 EE03973 B1 EE 03973B1 EE 9600146 A EE9600146 A EE 9600146A EE 9600146 A EE9600146 A EE 9600146A EE 03973 B1 EE03973 B1 EE 03973B1
Authority
EE
Estonia
Prior art keywords
activity
factor
compound
amino acids
provides
Prior art date
Application number
EE9600146A
Other languages
Estonian (et)
Other versions
EE9600146A (en
Inventor
Al-Obeidi Fahad
Lebl Michal
A. Ostrem James
Safar Pavel
Stierandova Alena
Strop Peter
Walser Armin
Original Assignee
Selectide Corporation
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Selectide Corporation filed Critical Selectide Corporation
Publication of EE9600146A publication Critical patent/EE9600146A/en
Publication of EE03973B1 publication Critical patent/EE03973B1/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/81—Protease inhibitors
    • C07K14/8107—Endopeptidase (E.C. 3.4.21-99) inhibitors
    • C07K14/811—Serine protease (E.C. 3.4.21) inhibitors
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
    • C07K5/0207—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-(X)4-C(=0), e.g. 'isosters', replacing two amino acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
    • C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06078—Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06086—Dipeptides with the first amino acid being basic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/08—Tripeptides
    • C07K5/0802—Tripeptides with the first amino acid being neutral
    • C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
    • C07K5/0806—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/08—Tripeptides
    • C07K5/0802—Tripeptides with the first amino acid being neutral
    • C07K5/0812—Tripeptides with the first amino acid being neutral and aromatic or cycloaliphatic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/08—Tripeptides
    • C07K5/0815—Tripeptides with the first amino acid being basic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/08—Tripeptides
    • C07K5/0821—Tripeptides with the first amino acid being heterocyclic, e.g. His, Pro, Trp
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/10—Tetrapeptides
    • C07K5/1002—Tetrapeptides with the first amino acid being neutral
    • C07K5/1005—Tetrapeptides with the first amino acid being neutral and aliphatic
    • C07K5/101—Tetrapeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/10—Tetrapeptides
    • C07K5/1002—Tetrapeptides with the first amino acid being neutral
    • C07K5/1016—Tetrapeptides with the first amino acid being neutral and aromatic or cycloaliphatic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/64—Cyclic peptides containing only normal peptide links
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/56—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving blood clotting factors, e.g. involving thrombin, thromboplastin, fibrinogen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Hematology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biotechnology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Neurosurgery (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Immunology (AREA)
  • Microbiology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Diabetes (AREA)
  • General Engineering & Computer Science (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

The invention provides compounds which specifically inhibit factor Xa activity. The compounds consist of the structure X 1 -YIR-X 2 , wherein X 1 is H, acyl, alkyl, acylalkyl, arylalkyl or one or more amino acids, and X 2 is a modified C-terminal group, one or more carboxy-protecting groups or one or more amino acids or other substituent, and Y, I and R are tyrosine, isoleucine and arginine, respectively, or peptidomimetic or organic structures that possess the same functional activity as Y, I and R, respectively. In addition, the present invention provides a compound having the structure A1-A2-(A3) m -B, where m is 0 or 1. A compound of the invention can be linear or cyclic and can be about 2 and 43 residues in length. A compound of the invention is characterized, in part, in that it exhibits a specific inhibition of factor Xa activity with a K i of ‰¤ 100 µM, preferably ‰¤ 2 nM, and does not substantially inhibit the activity of other proteases involved in the coagulation cascade. The invention further provides methods of specifically inhibiting the activity of factor Xa and of inhibiting blood clotting in vitro and in an individual and methods of detecting factor Xa levels or activity.
EE9600146A 1994-04-26 1995-04-25 Factor Xa inhibitors EE03973B1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US23305494A 1994-04-26 1994-04-26
PCT/US1995/005268 WO1995029189A1 (en) 1994-04-26 1995-04-25 FACTOR Xa INHIBITORS

Publications (2)

Publication Number Publication Date
EE9600146A EE9600146A (en) 1997-04-15
EE03973B1 true EE03973B1 (en) 2003-02-17

Family

ID=22875692

Family Applications (1)

Application Number Title Priority Date Filing Date
EE9600146A EE03973B1 (en) 1994-04-26 1995-04-25 Factor Xa inhibitors

Country Status (27)

Country Link
EP (2) EP0758341B1 (en)
JP (1) JP3655632B2 (en)
KR (1) KR100380124B1 (en)
CN (1) CN1181091C (en)
AT (1) ATE262536T1 (en)
AU (1) AU707653B2 (en)
CA (1) CA2186497C (en)
CZ (1) CZ296439B6 (en)
DE (1) DE69532754T2 (en)
DK (1) DK0758341T3 (en)
EE (1) EE03973B1 (en)
ES (1) ES2214500T3 (en)
FI (1) FI120494B (en)
HU (1) HUT76346A (en)
IL (1) IL113505A (en)
LT (1) LT4218B (en)
LV (1) LV11740B (en)
NO (1) NO318759B1 (en)
NZ (1) NZ284977A (en)
PL (1) PL188132B1 (en)
PT (1) PT758341E (en)
RU (1) RU2152954C1 (en)
SI (1) SI9520044B (en)
SK (1) SK286094B6 (en)
TW (1) TW409129B (en)
WO (1) WO1995029189A1 (en)
ZA (1) ZA953361B (en)

Families Citing this family (54)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EA199700186A1 (en) * 1995-02-17 1998-02-26 Басф Акциенгезельшафт NEW DIPEPTID AMIDINES USED AS THROMBIN INHIBITORS
US5747458A (en) * 1995-06-07 1998-05-05 Chiron Corporation Urokinase receptor ligands
US6069130A (en) 1995-06-07 2000-05-30 Cor Therapeutics, Inc. Ketoheterocyclic inhibitors of factor Xa
EP0868526B1 (en) * 1995-12-20 2002-08-14 Aventis Pharmaceuticals Inc. PROCESS FOR PREPARING N-ACETYL(L)-4-CYANOPHENYLALANINE Ac-(L)-Phe(4-CN)-OH AND N-ACETYL-(L)-p-AMIDINOPHENYLALANINE-CYCLOHEXYLGLYCINE-BETA-(3-N-METHYLPYRIDINIUM)-ALANINE Ac-(L)-pAph-Chg-PalMe(3)-NH2
US5766932A (en) * 1995-12-20 1998-06-16 Hoechst Marion Roussel, Inc. Process for preparing N-acetyl(L)-4-cyanophenylalanine from a mixture of the corresponding D,L ethyl esters using subtilisin
US6369080B2 (en) 1996-10-11 2002-04-09 Cor Therapeutics, Inc. Selective factor Xa inhibitors
US6262047B1 (en) 1996-10-11 2001-07-17 Cor Therapeutics, Inc. Selective factor Xa inhibitors
US6063794A (en) 1996-10-11 2000-05-16 Cor Therapeutics Inc. Selective factor Xa inhibitors
US6194435B1 (en) 1996-10-11 2001-02-27 Cor Therapeutics, Inc. Lactams as selective factor Xa inhibitors
EP0977773A1 (en) 1997-04-14 2000-02-09 Cor Therapeutics, Inc. SELECTIVE FACTOR Xa INHIBITORS
CA2285705A1 (en) * 1997-04-14 1998-10-22 Cor Therapeutics, Inc. Selective factor xa inhibitors
US6204268B1 (en) 1997-04-14 2001-03-20 Cor Therapeutics, Inc Selective factor Xa inhibitors
US7109326B2 (en) 1997-04-15 2006-09-19 Genentech, Inc. Halo-alkoxycarbonyl prodrugs
US6218382B1 (en) 1997-08-11 2001-04-17 Cor Therapeutics, Inc Selective factor Xa inhibitors
US6333321B1 (en) 1997-08-11 2001-12-25 Cor Therapeutics, Inc. Selective factor Xa inhibitors
US6228854B1 (en) 1997-08-11 2001-05-08 Cor Therapeutics, Inc. Selective factor Xa inhibitors
GB9727123D0 (en) * 1997-12-22 1998-02-25 Int Centre Genetic Eng & Bio Synthesis of diamines
PL195682B1 (en) 1997-12-24 2007-10-31 Sanofi Aventis Deutschland Derivatives of indole as inhibitors of factor xa
EP0987274A1 (en) * 1998-09-15 2000-03-22 Hoechst Marion Roussel Deutschland GmbH Factor VIIa Inhibitors
EP1016663A1 (en) * 1999-01-02 2000-07-05 Aventis Pharma Deutschland GmbH Novel malonic acid derivatives, processes for their preparation, their use and pharmaceutical compositions containing them (inhibition of factor Xa activity)
EP1022268A1 (en) * 1999-01-02 2000-07-26 Aventis Pharma Deutschland GmbH Arylalkanoyl derivatives, processes for their preparation, their use and pharmaceutical compositions containing them
ATE292114T1 (en) 1999-01-02 2005-04-15 Aventis Pharma Gmbh ARYL ALKANOYL DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF, THEIR USE AND PHARMACEUTICAL PREPARATIONS CONTAINING THEM
TR200101903T2 (en) * 1999-01-02 2001-11-21 Aventis Pharma Deutschland Gmbh New malonic acid derivatives, their preparation processes.
EP1059302A1 (en) * 1999-06-08 2000-12-13 Aventis Pharma Deutschland GmbH Factor VIIa inhibitors
EP1095933A1 (en) 1999-10-30 2001-05-02 Aventis Pharma Deutschland GmbH Novel N-guanidinoalkylamides, their preparation, their use, and pharmaceutical preparations comprising them
AU1890201A (en) * 1999-12-14 2001-06-25 Showa Denko Kabushiki Kaisha Process for producing salt of cyanobenzylamine or derivative
JP5088598B2 (en) * 1999-12-14 2012-12-05 昭和電工株式会社 Process for producing salts of cyanobenzylamines
WO2001055175A2 (en) 2000-01-28 2001-08-02 Aventis Pharma Deutschland Gmbh Process for the preparation of acetyl-amidiniophenylalanyl-cyclohexylglycyl-pyridinioalaninamides
EP1127884A1 (en) 2000-02-26 2001-08-29 Aventis Pharma Deutschland GmbH Novel malonic acid derivatives, processes for their preparation, their use as inhibitor of factor XA activity and pharmaceutical compositions containing them
DE10029015A1 (en) 2000-06-15 2001-12-20 Curacyte Ag Coagulation Factor Xa inhibitor, useful for treatment, prophylaxis or diagnosis of thromboembolic disease, comprising acylated 3- or 4-amidino-benzylamine derivative
ES2278798T3 (en) * 2000-12-06 2007-08-16 Sanofi-Aventis Deutschland Gmbh GUANIDINE AND AMIDINE DERIVATIVES IN QUALITY OF INHIBITORS OF FACTOR XA.
EP1314733A1 (en) 2001-11-22 2003-05-28 Aventis Pharma Deutschland GmbH Indole-2-carboxamides as factor Xa inhibitors
GB0130705D0 (en) * 2001-12-21 2002-02-06 Glaxo Group Ltd Chemical compounds
US7838560B2 (en) 2002-03-11 2010-11-23 The Medicines Company (Leipzig) Gmbh Urokinase inhibitors, production and use thereof
CN100513398C (en) 2002-12-03 2009-07-15 Axys药物公司 2- (2-hydroxybiphenyl-3-yl) -1H-benzimidazole-5-carboxamidine derivatives as factor VIIA inhibitors
US7358268B2 (en) 2002-12-04 2008-04-15 Sanofi-Aventis Deutschland Gmbh Imidazole derivatives as factor Xa inhibitors
GB0228533D0 (en) * 2002-12-06 2003-01-15 Glaxo Group Ltd Crystalline form
US7429581B2 (en) 2002-12-23 2008-09-30 Sanofi-Aventis Deutschland Gmbh Pyrazole-derivatives as factor Xa inhibitors
DE10301300B4 (en) 2003-01-15 2009-07-16 Curacyte Chemistry Gmbh Use of acylated 4-amidino- and 4-guanidinobenzylamines for the inhibition of plasma kallikrein
US7741341B2 (en) 2003-05-19 2010-06-22 Sanofi-Aventis Deutschland Gmbh Benzimidazole-derivatives as factor Xa inhibitors
US7317027B2 (en) 2003-05-19 2008-01-08 Sanofi-Aventis Deutschland Gmbh Azaindole-derivatives as factor Xa inhibitors
US7223780B2 (en) 2003-05-19 2007-05-29 Sanofi-Aventis Deutschland Gmbh Triazole-derivatives as blood clotting enzyme factor Xa inhibitors
EP1479675A1 (en) 2003-05-19 2004-11-24 Aventis Pharma Deutschland GmbH Indazole-derivatives as factor Xa inhibitors
EP1479677A1 (en) 2003-05-19 2004-11-24 Aventis Pharma Deutschland GmbH New indole derivatives as factor xa inhibitors
EP1479680A1 (en) 2003-05-19 2004-11-24 Aventis Pharma Deutschland GmbH Azaindole derivatives as Factor Xa inhibitors
DE10342108A1 (en) 2003-09-11 2005-04-14 Curacyte Chemistry Gmbh Basic substituted benzylamine analogs as coagulation factor Xa inhibitors, their preparation and use
EP1568698A1 (en) 2004-02-27 2005-08-31 Aventis Pharma Deutschland GmbH Pyrrole-derivatives as factor Xa inhibitors
US7446210B2 (en) 2004-10-26 2008-11-04 Janssen Pharmaceutica N.V. Factor Xa compounds
EP1724269A1 (en) 2005-05-20 2006-11-22 Sanofi-Aventis Deutschland GmbH Heteroaryl-carboxylic acid (sulfamoyl alkyl) amide - derivatives as factor Xa inhibitors
DE102005044319A1 (en) 2005-09-16 2007-03-22 Curacyte Chemistry Gmbh 2- (Aminomethyl) -5-chloro-benzylamide derivatives and their use as inhibitors of coagulation factor Xa
DE102006050672A1 (en) 2006-10-24 2008-04-30 Curacyte Discovery Gmbh New glycylglycine derivatives with a benzylsulfonylamido group and an amidino-organylamido group at the opposite chain ends, used in drugs for reducing loss of blood, e.g. in operations
EP1918718A1 (en) * 2006-10-31 2008-05-07 Roche Diagnostics GmbH Methods and devices for electrochemical determination of factor Xa inhibitors in blood samples
AU2008239659B2 (en) 2007-04-13 2013-09-05 Millennium Pharmaceuticals, Inc. Combination anticoagulant therapy with a compound that acts as a factor Xa inhibitor
DE102023133734A1 (en) 2023-12-01 2025-06-05 Technische Universität Darmstadt, Körperschaft des öffentlichen Rechts Rapid determination of analyte levels

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4275153A (en) * 1978-08-03 1981-06-23 American Hospital Supply Corporation Analytical fluorogenic substrates for proteolytic enzymes
CA1161431A (en) * 1979-05-11 1984-01-31 Lars G. Svendsen Tripeptide derivatives
US4469679A (en) * 1983-02-16 1984-09-04 Smithkline Beckman Corporation Octapeptide vasopressin antagonists
HU191961B (en) * 1984-08-02 1987-04-28 Richter Gedeon Vegyeszet Process for producing 1,5 and 8 substituted peptides of angiotenzin-ii antagonistic activity
CA2008116C (en) * 1989-02-23 2001-11-20 Thomas Weller Glycine derivatives
HU206372B (en) * 1990-09-03 1992-10-28 Richter Gedeon Vegyeszet Process for producing new oligopeptides which selectively inhibit proliferation of haemopoietic cells and pharmaceutical compositions comprising same
WO1993015756A1 (en) * 1992-02-14 1993-08-19 Corvas International, Inc. Inhibitors of thrombosis

Also Published As

Publication number Publication date
LT96151A (en) 1997-05-26
AU2368395A (en) 1995-11-16
HUT76346A (en) 1997-08-28
EP0758341A1 (en) 1997-02-19
SI9520044B (en) 2004-08-31
AU707653B2 (en) 1999-07-15
NO318759B1 (en) 2005-05-02
RU2152954C1 (en) 2000-07-20
IL113505A (en) 1999-12-31
WO1995029189A1 (en) 1995-11-02
PL188132B1 (en) 2004-12-31
CN1147261A (en) 1997-04-09
NO964553L (en) 1996-12-27
EP0758341B1 (en) 2004-03-24
EP1384725A2 (en) 2004-01-28
DK0758341T3 (en) 2004-06-28
ZA953361B (en) 1996-01-12
DE69532754T2 (en) 2005-03-10
LV11740B (en) 1997-12-20
SI9520044A (en) 1997-10-31
JP3655632B2 (en) 2005-06-02
FI964317A0 (en) 1996-10-25
PT758341E (en) 2004-08-31
SK136696A3 (en) 1997-05-07
FI120494B (en) 2009-11-13
CA2186497A1 (en) 1995-11-02
CZ296439B6 (en) 2006-03-15
NZ284977A (en) 1998-09-24
FI964317A7 (en) 1996-10-25
PL317067A1 (en) 1997-03-03
IL113505A0 (en) 1995-07-31
ES2214500T3 (en) 2004-09-16
ATE262536T1 (en) 2004-04-15
CZ314096A3 (en) 1997-05-14
SK286094B6 (en) 2008-03-05
TW409129B (en) 2000-10-21
EP1384725A3 (en) 2007-02-21
LT4218B (en) 1997-09-25
DE69532754D1 (en) 2004-04-29
CA2186497C (en) 2008-06-17
CN1181091C (en) 2004-12-22
JPH10503477A (en) 1998-03-31
LV11740A (en) 1997-04-20
NO964553D0 (en) 1996-10-25
HU9602954D0 (en) 1996-12-30
EE9600146A (en) 1997-04-15
KR100380124B1 (en) 2003-08-02

Similar Documents

Publication Publication Date Title
FI964317A0 (en) Factor Xa inhibitors
ATE102629T1 (en) PEPTIDE DERIVATIVES OF PLATELET AGGREGATION INHIBITOR.
DE69729583D1 (en) N- (AMIDINOPHENYL) -N '- (SUBST.) - 3H-2,4-BENZODIAZEPIN-3-ON DERIVATIVE AS FACTOR XA INHIBITORS
NZ500620A (en) Synthetic peptides which inhibit serine proteases, specifically thrombin, factor VIIa tissue factor and factor Xa
DE69717268D1 (en) M-AMIDINOPHENYL ANALOGUE AS FACTOR XA INHIBITORS
UA32556C2 (en) (1r, 4ar, 8ar)-1,2,3,4,5,6,7,8-perhydroisoquinolin-1-carbonyl-(l)-prolinyl-(l)-arginine aldehyde useful as an thromboembolic disorder agent and pharmaceutical composition
SE9602263D0 (en) New amino acid derivatives
FI942625A7 (en) Peptide phosphinyloxymethyl ketones as inhibitors of interleukin-1beta-converting enzyme
ATE181925T1 (en) INHIBITORS FOR CATHEPSIN-G AND ELASTASE TO PREVENT CONNECTIVE TISSUE DEGRADATION
ATE153670T1 (en) PEPTIDEBORONIC ACID DERIVATIVES WITH PROTEASE INHIBITING ACTIVITY
EA200000204A1 (en) Pyrrolopyrlonone derivatives as ELASTASIS INHIBITORS NEUTROPHILS
ES2168816T3 (en) INJECTION CEMENT CONTAINING CORROSION INHIBITORS.
ATE289319T1 (en) DIPEPTIDIC INHIBITORS FOR THE CLOTTING FACTOR XA
MX9605037A (en) FACTOR Xa INHIBITORS.
ATE205506T1 (en) FACTOR IX BINDING PEPTIDES DERIVED FROM FACTOR VII AND THEIR USE AS BLOOD CLOTTING INHIBITORS
ATE292682T1 (en) SERINE PROTEINASE INHIBITORS
DE68908958D1 (en) Peptides.
ATE362545T1 (en) SCREENING PROCEDURE FOR SUBSTANCES FOR THE TREATMENT OF DIABETES
RU94037136A (en) Imidazole-containing inhibitors of cathepsin-g-induced platelet aggregation
NO950255D0 (en) Use of alpha, omega-dicarboxylic acids as fibrinogen reducing agents
TH38361A (en) Serine protease inhibitors
HUP9601528A2 (en) Peptide derivatives of anticoagulant activity and pharmaceutical compositions containing them

Legal Events

Date Code Title Description
KB4A Valid patent at the end of a year

Effective date: 20031231

KB4A Valid patent at the end of a year

Effective date: 20041231

KB4A Valid patent at the end of a year

Effective date: 20051231

KB4A Valid patent at the end of a year

Effective date: 20061231

KB4A Valid patent at the end of a year

Effective date: 20071231

KB4A Valid patent at the end of a year

Effective date: 20081231

KB4A Valid patent at the end of a year

Effective date: 20091231

KB4A Valid patent at the end of a year

Effective date: 20101231

MM4A Lapsed by not paying the annual fees

Effective date: 20110425